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In vivo model of human post-traumatic heterotopic ossification demonstrates early fibroproliferative signature.
de Vasconcellos, Jaira F; Zicari, Sonia; Fernicola, Stephen D; Griffin, Daniel W; Ji, Youngmi; Shin, Emily H; Jones, Patrick; Christopherson, Gregory T; Bharmal, Husain; Cirino, Carl; Nguyen, Thao; Robertson, Astor; Pellegrini, Vincent D; Nesti, Leon J.
Afiliación
  • de Vasconcellos JF; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Zicari S; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
  • Fernicola SD; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Griffin DW; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
  • Ji Y; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Shin EH; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Jones P; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Christopherson GT; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Bharmal H; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Cirino C; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Nguyen T; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Robertson A; Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
  • Pellegrini VD; Department of Orthopaedic Surgery, University of Maryland Medical Center, 22 S. Green St., Baltimore, MD, 21201, USA.
  • Nesti LJ; Department of Orthopaedic Surgery, University of Maryland Medical Center, 22 S. Green St., Baltimore, MD, 21201, USA.
J Transl Med ; 17(1): 248, 2019 08 02.
Article en En | MEDLINE | ID: mdl-31375141
ABSTRACT

BACKGROUND:

The relationship between the tissue injury healing response and development of heterotopic ossification (HO) is poorly understood. Here we compare a rat blast model and human traumatized muscle from a blast injury to study the early signatures of osteogenesis and fibrosis during the formation of HO.

METHODS:

Rat and human tissues were characterized using histology, scanning electron microscopy, immunohistochemistry, as well as gene and protein expression analysis. Additionally, animals and humans were assessed radiographically for HO formation following injury.

RESULTS:

Markers of bone formation were dramatically increased in tissue samples from both humans and rats, and both displayed increased fibroproliferative regions within the injured tissues and elevated expression of markers of tissue fibrosis such as TGF-ß1, Fibronectin, SMAD3 and PAI-1. Markers of inflammation and fibrosis (ACTA, TNFα, BMP1 and BMP3) were elevated at the RNA level in both rat and human samples. By day 42, bone formation in the rat blast model appeared similar in radiographs compared to human patients who progressed to develop post-traumatic HO.

CONCLUSIONS:

Our data demonstrates that a similar early fibrotic response is evident in both the rat blast model and the human tissues following a traumatic injury and demonstrates the relevance of this animal model for future translational studies.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Traumatismos por Explosión / Osificación Heterotópica / Músculos Límite: Animals / Humans / Male Idioma: En Revista: J Transl Med Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Traumatismos por Explosión / Osificación Heterotópica / Músculos Límite: Animals / Humans / Male Idioma: En Revista: J Transl Med Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos